A neonatal thymic factor (NTF) has been shown in our laboratory to have significant immunostimulatory effects upon lymphocytes of adult thymectomized and normal aged mice as assayed by response to T-cell mitogens and in the mixed lymphocyte reaction. We shall attempt to elucidate the specific subpopulation of T-cells in the aged mouse which is susceptible to NTF. To avail ourselves of selected sources of activity involving these subpopulations we shall employ a variety of physical procedures and functional assays, including (1) nylon wool column separation, (2) response to selective T-cell mitogens, (3) mixed lymphocyte reactivity, and (4) cell-mediated lymphocytotoxicity. NTF enhancement of synergizing capacity between T-cell subpopulations in aged mice as well as its potential to alter age-related suppressor cell function will be determined using the mixed lymphocyte reaction. With trends now established associating T-cell deficiency with increased autorecognition, we shall also test the ability of NTF to regulate autoreactivity in the thymectomized and normal aged mouse. This shall be accomplished using syngeneic to 51-Cr-labelled TNP-modified spleen cells as targets, and primed spleen cells from aged or thymectomized mice as effector cells. In this system, the syngeneic hapten-modified spleen cells may be considered a modified self or auto-antigen. Treatment of effector cells with NTF either in vivo or in vitro, during priming and effector phases, may induce control of autoreactivity, as manifested by an inhibition of cytotoxicity against modified-self antigens.